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Influenza virus infection remains a major health concern due to morbidity and mortality associated with epidemics and occasional pandemics. The absence of acquired immunity to antigenically distinct, emerging virus strains stresse...
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Influenza virus infection remains a major health concern due to morbidity and mortality associated with epidemics and occasional pandemics. The absence of acquired immunity to antigenically distinct, emerging virus strains stresses the need for a generic drug that protects independent of vaccination. Here, we demonstrate that prophylactic administration of chitin microparticles (CMP) via the intranasal route significantly reduced lung viral titres and clinical signs. Pre-treatment boosted the innate immune response to subsequent infection by recruiting innate cells, such as neutrophils, and increasing inflammatory cytokines. Although an increase in virus-specific T cells was observed, the memory phase was diminished. Our data demonstrate that in the absence of prior exposure to influenza virus. CMP reduce clinical signs by boosting innate immunity.
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Adenoviruses are the most commonly used vectors for gene therapy. Despite the promising safety profile demonstrated in clinical trials, the efficacy of using adenoviruses for gene therapy is poor. A major hurdle to adenoviral-medi...
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Adenoviruses are the most commonly used vectors for gene therapy. Despite the promising safety profile demonstrated in clinical trials, the efficacy of using adenoviruses for gene therapy is poor. A major hurdle to adenoviral-mediated gene therapy is the innate immune system. Cell-mediated recognition of viruses via capsid components or nucleic acids has received significant attention, principally thought to be regulated by the toll-like receptors (TLRs). Antiviral innate immune responses are initiated by the infected cell, which activates the interferon (IFN) response to block viral replication, while simultaneously releasing chemokines to attract neutrophils, mononuclear- and natural killer-cells. While the IFN and cellular recruitment pathways are activated and regulated independently of each other, both are required to overcome immune escape mechanisms by adenoviruses. Recent work has shown that the generation of adenoviral vectors lacking specific transcriptionally-active regions decreases immune system activation and increases the chance for immune escape. In this review, we elucidate how adenoviral vector modifications alter the IFN and innate inflammatory pathway response and propose future targets with clinically-translational relevance.
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Heat shock proteins (HSPs) are highly effective and versatile molecules in promoting antitumor immune responses. We tested whether a HSP-based DNA vaccine can induce effective immune response against Mage3, a cancer testis (CT) an...
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Heat shock proteins (HSPs) are highly effective and versatile molecules in promoting antitumor immune responses. We tested whether a HSP-based DNA vaccine can induce effective immune response against Mage3, a cancer testis (CT) antigen frequently expressed in many human tumors, thereby controlling the Mage3-expressing tumor. The vaccine was constructed by linking human inducible HSP70 to the C-terminus of a modified Mage3 gene (sMage3) that was attached at its N-terminus with the signal leader sequence of the human RANTES for releasing the expressed fusion protein from the transduced cells. Intramuscular injection of sMage3Hsp DNA induced CD4(+)/CD8(+) T cell and antibody responses. Vaccination with sMage3Hsp DNA was more effective in inhibiting Mage3-expressingTC-1 tumors. When we dissected the antitumor activity of CD4(+) and CD8(+) T cells by immunizing CD4(+) and CD8(+) knockout mice with sMage3Hsp DNA, we found that both CD8(+) T and CD4(+) T cells played a role in control of inoculated tumor, but did not constitute the whole of immune protection in the prophylactic immunization. Instead, depletion of natural killer (NK) cells led to a major loss of antitumor activity in the immunized mice. These results indicate that the HSP-based Mage3 DNA vaccine can more effectively inhibit tumor growth by inducing both the innate immune responses and Mage3-specific adaptive immune responses via the Hsp-associated adjuvant function.
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Neisseria gonorrhoeae is an exclusive human pathogen that causes the sexually transmitted disease, gonorrhea. The gonococcus has developed an exquisite repertoire of mechanisms by which it is able to evade host innate and adaptive...
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Neisseria gonorrhoeae is an exclusive human pathogen that causes the sexually transmitted disease, gonorrhea. The gonococcus has developed an exquisite repertoire of mechanisms by which it is able to evade host innate and adaptive immune responses. Our previous data indicate that the predominately asymptomatic nature of gonococcal cervicitis may, in part, be attributed to the ability of these bacteria to subvert the normal function of complement to promote cervical disease. Herein we describe the interaction of N. gonorrhoeae with the complement alternative pathway with a particular focus on the importance of this interaction in promoting gonococcal cervicitis. (C) 2008 Elsevier Ltd. All Fights reserved.
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The Helicobacter pylori infections are followed by an infiltration of the gastric mucosa by neutrophils and macrophages. Accumulation of phagocytes enables them to interact with H. pylori, but a great number of infected subjects c...
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The Helicobacter pylori infections are followed by an infiltration of the gastric mucosa by neutrophils and macrophages. Accumulation of phagocytes enables them to interact with H. pylori, but a great number of infected subjects cannot eradicate these bacteria. The H. pylori inhibits its own uptake by blocking the function of phagocytes. The anti-phagocytic mechanism depends on bacterial surface structures and the presence of the cag pathogenicity island (PAI). The role of H. pylori lipopolysaccharide (LPS), during phagocytosis of these bacteria is not clear. LPS may mediate direct bacteria/phagocyte interactions and it may also regulate antibacterial activity of the phagocytes. In this study we investigated the influence of H. pylori LPS on phagocytosis of these bacteria. The H. pylori LPS inhibited an ingestion of these microbes by human peripheral blood granulocytes. This was correlated with a diminished ability of phagocytes to reduce MTT-tetrazolium salt. The anti-phagocytic effect of H. pylori LPS was reduced by recombinant lipopolysaccharide binding protein (rLBP). It is possible that in vivo H. pylori LPS may diminish elimination of these bacteria from the gastric mucosa promoting an infection persistence. However, LBP may modulate the uptake of H. pylori due to neutralization of anti-phagocytic effect of its LPS.
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P>Currently, little information is available regarding innate immunity to helminthic parasite infection. In this study, we isolated the excretory-secretory (ES) proteins from Anisakis simplex (sea mammal intestinal parasite) third...
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P>Currently, little information is available regarding innate immunity to helminthic parasite infection. In this study, we isolated the excretory-secretory (ES) proteins from Anisakis simplex (sea mammal intestinal parasite) third stage larva. We determined that the levels of IL-17 in the lung and lung draining lymph node of mice were increased sixfold as a result of intranasal treatment with ES proteins. The ES protein treatment elicited pro-inflammatory cytokine and chemokine secretion (especially IL-6 and CXCL1) from mouse lung epithelial cell line and primary lung epithelial cells. In addition, the expression of IL-6 and CXCL1 in mouse embryonic fibroblast (MEF) cells was significantly increased by the ES protein treatment, but we did not detect these effects in the TRIF-/- MEF cells. These elevations of IL-6 and CXCL1 expression were also not diminished by RNase treatment. In conclusion, the ES proteins of helminthic parasite larva may elicit TRIF dependent pro-inflammatory cytokines, and this is not double-stranded RNA.
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The understanding of innate immune modulation by pathogens and immune-modulating agents, including synthetic oligodeoxynucleotides (CpG ODNs), has offered several new approaches to improve prophylactic and therapeutic strategies a...
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The understanding of innate immune modulation by pathogens and immune-modulating agents, including synthetic oligodeoxynucleotides (CpG ODNs), has offered several new approaches to improve prophylactic and therapeutic strategies against infectious diseases in humans and animals. However, in this regard not much work has been done in avian medicine. In the present study, we analyzed the kinetics of interferon (IFN), cytokine, and chemokine mRNA expression in chicken embryonic spleen at 6 hr, 24 hr, 48 hr, and 72 hr after administration of CpG ODN 2007 (B-class) in 18-day-old chicken embryos. Our data showed enhanced expression of IFN-gamma; interleukin (IL)-1 beta, IL-6, and IL-8; and oligoadenyl synthetase A mRNA after CpG ODN administration. In addition, CpG ODN administration to chicken embryos 24 hr before the challenge with infectious bronchitis virus (IBV) was capable of limiting IBV propagation in different embryonic tissues. Based on the kinetics and type of cytokines induced after in ovo administration of CpG ODN, it may be speculated that in ovo administration of CpG ODNs may enhance resistance from viral infection in neonatal chicks and that CpG ODNs may contribute toward the development of more effective and safer poultry vaccines including in ovo vaccines.
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C-type lectins may function as pattern-recognition receptors (PRRs) and play important roles in immune responses. In this work, a cDNA for a new C-type lectin, FcLec3, was obtained from Chinese white shrimp Fenneropenaeus chinensi...
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C-type lectins may function as pattern-recognition receptors (PRRs) and play important roles in immune responses. In this work, a cDNA for a new C-type lectin, FcLec3, was obtained from Chinese white shrimp Fenneropenaeus chinensis using expressed sequence tag analysis and rapid amplification of the cDNA ends. FcLec3 contains an N-terminal signal peptide and a carbohydrate recognition domain (CRD). RT-PCR analysis showed that FcLec3 was mainly expressed in hepatopancreas and that the expression of FcLec3 was obviously up-regulated by Vibrio anguillarum or white spot syndrome virus (WSSV) challenge. Recombinant FcLec3 could agglutinate Gram-negative and -positive bacteria with the presence of calcium. A following agglutination inhibitory test indicated that FcLec3 could recognize muramic acid and peptidoglycan. Besides, pull-down assay showed that the recombinant protein could interact with VP28, one major envelope protein of WSSV. These results suggested that FcLec3 might function in the recognition of bacterial and viral pathogens in shrimp.
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The NS1 protein of influenza A viruses is known as a nonessential virulence factor inhibiting type 1 interferon (IFN) production in mammals and in chicken cells. Whether NS1 inhibits the induction of type I IFNs in duck cells is c...
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The NS1 protein of influenza A viruses is known as a nonessential virulence factor inhibiting type 1 interferon (IFN) production in mammals and in chicken cells. Whether NS1 inhibits the induction of type I IFNs in duck cells is currently unknown. In order to investigate this issue, we used reverse genetics to generate a virus expressing a truncated NS1 protein. Using the low pathogenic avian influenza virus A/turkey/Italy/977/1999 (H7N1) as a backbone, we were able to rescue a virus expressing a truncated NS1 protein of 99 amino acids in length. The truncated virus replicated poorly in duck embryonic fibroblasts, but reached high titers in the mammalian IFN-deficient Vero cell line. Using a gene reporter system to measure duck type 1 IFN production, we showed that the truncated virus is a potent inducer of type I IFN in cell culture. These results show that the NS1 protein functions to prevent the induction of IFN in duck cells and underline the need for a functional NS1 protein in order for the virus to express its full virulence.
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The work presented here describes the construction of plasmid encoding the VP2 gene of the infectious pancreatic necrosis virus (IPNV), its expression in BF-2 cells and an evaluation of its activity in brown trout (Salmo trutta L)...
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The work presented here describes the construction of plasmid encoding the VP2 gene of the infectious pancreatic necrosis virus (IPNV), its expression in BF-2 cells and an evaluation of its activity in brown trout (Salmo trutta L) soon after injection. Preliminary experiments to evaluate the potential of the plasmid to induce neutralizing antibodies were also performed. We established a BF-2 cell line that expresses VP2 constitutively and we examined the infection of these VP2-transfected BF-2 cells with homologous and heterologous; viruses. The expression kinetics of IFN, and of the IFN-induced genes Mx and ISG15, was also evaluated in brown trout over a 15 day interval, and quantified by real-time or semi-quantitative PCR. Type I IFN and Mx are markers of the non-specific innate immune response to viruses and they are involved in antiviral defences. Our results demonstrate that expression of the IPNV VP2 protein in BF-2 cells induces an antiviral state against IPNV and against the infectious haematopoietic necrosis virus (IHNV). In BF-2 infected cells, VP2 inhibited both the IPNV and IHNV-induced cytopathic effect to some extent, as well as the virus yield. In vivo, VP2 was expressed in haematopoietic tissues such as the head kidney of 7 month-old trout. In addition, it induced early immune responses and specific immunity 30 days after injection. IFN mRNA expression increased sharply on the 1st and 15th day post-injection and expression of other IFNI-induced genes as Mx and ISG15 was also detected soon after vaccination of brown trout. Moreover, specific antibodies were detected 30 days after vaccination. These results suggest that the VP2 gene is a good candidate for the design of IPNV-DNA vaccines and to investigate the use of cytokines as co-stimulatory molecules.
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